Cu- Catalyzed ynthesis of Diaryl Thioethers and - Cycles by reaction of Aryl odides with Carbon Disul;ide in the Presence of DBU. Peng Zhao, Hang Yin, Hongxin, Gao, Chanjuan Xi.; J. rg. Chem. ArCcle AAP D: 10.1021/jo400709s James Johnson Current Literature 5/11/2013
Diarylthioethers Diarylthioethers have shown accvity against cancer, HV, Alzheimer s disease, inflammacon, and asthma. ElectronegaCvity and Bonding xygen 3.44 ulfur 2.58 N Ar AZD4407 1.4A Ar Ar 110 100 H 5c N H 1.75A Ar The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. estart your computer, and then open the file again. f the red x still appears, you may have to delete the image and then insert it again. 2 Molecules 2011, 16, 590-608 Top rganomet Chem (2010) 31: 39 64 Tetrahedron 1984, 40, 1433.
Palladium Catalyzed - Arylation - 8 mol% Pd(PPh 3 ) 4 H, 3h, reflux 36-93% 15 examples X -H X=Br, Cl Cl Ar-H Ar-H 2 mol% Pd(Ac) 2 DiPPF, t-buna dioxane 18h, 100 C 70-90% 8 examples 2 mol% Pd Josiphos, t-buna Toluene, 110 C 70-99% 11 examples 2 mol% Pd/C KH DM, 110 C 65-99% 14 examples Ar Ar 3 Bull. Chem. oc. Jpn. 1980, 53, 1385. JC. 2004, 69, 3236-3239 Chem. Eur. J. 2006, 12, 7782 7796 Adv. ynth. Catal. 2009, 351, 2558 2562
Cu Catalyzed - Arylation X H K 2 C 3 X=, Br, Cl, F DMF, 135 C 24h Br 1) nbuli, -78 C, THF 2) 8 B(H) 2 Tet Lec 39 (1998) 6283-6286 J. rg. Chem. 2004, 69, 3236-3239 J. rg. Chem. 2012, 77, 2878 2884 J. rg. Chem. 2008, 73, 5625 5628 H Ar-H -H 3) X 71-96% 17 examples Cu(Ac) 2 (1.5 eq) pyridine 4A M, DMF 40-90% 2.5 mol% Cu K 2 C 3 2eq NMP, 6 h, 100 C 46-96% 8 examples 5 mol% Cu 2 eq. HCH 2 CH 2 H 2 eq. K 2 C 3 iprh,18-22h, 80 C 82-93% 10 examples Ar = Ar, Alkyl 4
-H Cu Catalyzed - Arylation Cu 10 mol% 10 mol% tripod ligand Cs 2 C 3 DMF: dioxane(1:9) 24h, 110 C H H Cu H Ar-H 10 mol% CuBr Ligand, Cs 2 C 3 DM, 24h, 60 C Ar L B(H) 2 H H B(H) 2 N 5 mol% Cu 4 1, 10-Phen.H 2 (5 mol%) nbu 4 NH(40%aq.) H, rt, 8h, 2 41-85% 50 examples Cu 10 mol% Neocuproine 10 mol% 1.5eq. Nat-Bu Toluene, 110 C 81-97% 16 examples CuMeal (20-30 mol%) THF, 45-50 C 2-12h 56-83% 13 examples N N 1, 10-Phen. N N Neocuproine H Meal 5 rg. Lec., 2002, 4,. 20, 3517 rg. Lec., 2002l. 4,. 16, 2803-2806
ther Metal Catalyzed - arylation X X=, Br -H 1 mol% Co 2 (dppe) Zn (1.5eq), pyr CH 3 CN, 10h, 80 C 29-98% 22 examples Ar-H Ar-H Ar-H 10 mol% FeCl 3 20 mol% DMEDA NatBu Toluene, 24h, 135 C 10 mol% FeCl 3 10 mol% BNAP NatBu Toluene, 24h, 135 C [(Pr)Ni(allyl)Cl] Nat-Bu DMF, 24h, 100 C Ar Ar Ar 33-98% 18 examples 72-95% 12 examples 76-99% 13 examples 6 rg. Lec., Vol. 8, No. 24, 2006 Chem. Commun., 2009, 4450 4452 Angew. Chem. nt. Ed. 2008, 47, 2880 2883 rg. Le=. 2007, 9, 3495-3498
s it Fe or Cu? 7 Angew. Chem. nt. Ed. 2009, 48, 5586-5587.
Nanoparticles -H 3 mol% Cu np KH 1.5 eq. DM, 24h, 135 C 88-99% 7 examples -H -H 1 mol% Cu on mseoporous i 2 Cs 2 C 3 dioxane, 21h, 110 C 3 mol% n 2 3 np KH 2 eq. DM, 24h, 135 C 65-96% 24 examples 56-97% 15 examples recyclable catalyst 8 Angew. Chem., nt. Ed. 2007, 46, 5583. Chem. Commun. 2010, 46, 282. rg. Lec. 2009, 11, 1697.
Previous work 9 rg. Lec., 2010, 12, 17, 3930
Title Paper 10 D: 10.1021/jo400709s
ptimization 11 D: 10.1021/jo400709s
Catalytic Cycle 12 J. Acta Crystallogr. 1986, C42, 487. Published in: Peng Zhao; Hang Yin; Hongxin Gao; Chanjuan Xi; J. rg. Chem. ArCcle AAP D: 10.1021/jo400709s
10 mol% Cu DBU, C 2 Toluene, 100 C 12h Yield Yield Yield Yield H 85% 2- NMe 2 78% 2- Me 83% 4- Ph 56% 4- Me 80% 2- H 81% 2- Me 75% 2,4- Me 70% 3- Me 65% 4- Me 68% 2- Br 65% 2,5- Me 68% 4- Br 74% 3- C 2 Me 65% 4- C 2 Me 65% 2,4,6- Me 50% 4- Cl 70% 4- CF 3 78% 1- Nap 84% 4- Pyr 75% 2- Pyr 66% 2- Thiophene 70% 13
ntramolecular C- - C formation Ar Ar 10 mol% Cu DBU, C 2 Toluene, 100 C 12h Ar Ar N H H 75% N 62% 65% Bu Ph 74% Bu 68% 78% Ph 14 72%
Conclusions ntramolecular coupling of two aryl iodides to form a diaryl thioether. FuncConal group tolerant. Cu $.23/g, Pd(Ac) 2 $94/g, FeCl 3 $.26/g Homocoupling applicacon C 2 inexpensive and easy to use 15 Alfa Aesear Top rganomet Chem (2010) 31: 39 64 Tetrahedron 1984, 40, 1433.
Previous work: 16 JC. 2012, 77, 4148 4151 rg. Lec., 2010, 12, 17, 3930 Tet Lec 54 (2013) 2357 2361
Previous work: 17 JC. 2012, 77, 4148 4151 rg. Lec., 2010, 12, 17, 3930 Tet Lec 54 (2013) 2357 2361
Palladium catalytic cycle 18
Chan Lam Catalytic cycle 19
Cobalt Catalyzed 20
21 Published in: Peng Zhao; Hang Yin; Hongxin Gao; Chanjuan Xi; J. rg. Chem. ArCcle AAP D: 10.1021/jo400709s Copyright 2013 American Chemical ociety
22 J. Med. Chem. 2005, 48, 2892-2905